Recovery from Friend virus (FV)-induced erythroleukemia in mice is influenced by two H-2-linked genes, Rfv-1 and Rfv-2, and one non-H-2 associated gene, Rfv-3. The Rfv-1 and Rfv-2 genes have now been found to influence the virus-specific T lymphocyte response. The Rfv-2 gene has been mapped to the I region of the H-2 complex and appears to function as a dominant immune response gene. The Rfv-1 gene, located in the D region of H-2, influences the kinetics of development of the FV-specific T lymphocyte proliferative response. Previous assays for FV-specific T lymphocyte function such as cell-mediated cytotoxicity were always negative in mice which had not recovered. However, the use of an in vitro T lymphocyte proliferation test was able to detect a positive response in some mouse strains even in the presence of leukemic splenomegaly. Using this test, mice with the high recovery genotype (H-2Db/b) had a positive T lymphocyte response 6-10 days earlier than mice with the low recovery genotype (H-2Ddb). This result was also supported by the fact that adoptive transfer of immune T lymphocytes induced recovery from leukemia in H-2Dd/b mice only if transferred early after virus inoculation. Thus, the delay in the development of the FV-specific T lymphocyte response of H-2Dd/b mice apparently allowed the virus-induced leukemia to progress to the point where the leukemia could no longer be eliminated by the intrinsic T lymphocyte response or by passively transferred immune T lymphocytes. The Rfv-3 gene influences production of anti-FV antibody, and has been found to be necessary but not sufficient for recovery from leukemia. However, in the absence of the appropriate Rfv-1 (H-2Db/b) genotype, Rfv-3r/s mice still make antibody which leads to elimination of FV viremia and marked reduction in virus release by leukemic spleen cells. Recent results using passive transfer of monoclonal antibodies showed that the Rfv-3 gene effects could be mimicked only by anti-gp70 antibodies of the IgG2a subclass. These antibodies appeared to mediate selection and overgrowth of spontaneously arising virus nonproducer cells in the leukemic spleen cell populations.